PCSK9 Antibodies in Adults With Hypercholesterolemia | Journal Scan

Study Questions:

What is the efficacy and safety of proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies [PCSK9 inhibition (PCSK9i)] in adults with hypercholesterolemia?

Methods:

The authors searched MEDLINE, PubMed Central, and Google Scholar; conference proceedings; and the ClinicalTrials.gov registry through April 4, 2015. They included Phase 2 or 3 randomized controlled trials (RCTs) comparing treatment using PCSK9i with no anti-PCSK9 therapy in adults with hypercholesterolemia. Prespecified primary endpoints were all-cause and cardiovascular mortality. Treatment and placebo control groups could be on ezetimibe, statins, or combination of both.

Results:

Twenty-four RCTs comprising 10,159 patients were included. Compared with no antibody, treatment with PCSK9i led to marked reductions in low-density lipoprotein cholesterol (mean difference, -47.49%; 95% confidence interval, -69.64% to -25.35%; p < 0.001), 25% reduction in lipoprotein (a), and about a 6% increase in high-density lipoprotein cholesterol. While overall mortality was very low at 0.39%, active treatment reduced all-cause mortality (odds ratio [OR], 0.45; p = 0.015) and cardiovascular mortality (OR, 0.50; p = 0.084). The rate of myocardial infarction was significantly reduced with use of PCSK9i (OR, 0.49; p = 0.030), and increases in the serum creatine kinase level were reduced (OR, 0.72; p = 0.026). Serious adverse events did not increase with administration of PCSK9 inhibition.

Conclusions:

The authors concluded that PCSK9 antibodies seem to be safe and effective for adults with dyslipidemia.

Perspective:

The summary of available literature supports the safety and lack of adverse events with PCSK9 inhibitors in over 10,000 patients who were followed from 2 months to 2 years. Longer-term data in well-defined populations will be necessary to establish safety and appropriate clinical use of this expensive novel class of lipid-lowering agents.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Advanced Lipid Testing, Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Nonstatins, Novel Agents, Statins

Keywords: Azetidines, Cholesterol, Cholesterol, LDL, Cholesterol, HDL, Control Groups, Creatine Kinase, Dyslipidemias, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypercholesterolemia, Lipoprotein(a), Lipoproteins, HDL, Lipoproteins, LDL, Myocardial Infarction, Proprotein Convertases, Subtilisins, Primary Prevention


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